AB0239 THE REDUCTION OF CIRCULATING LEVELS OF SERUM CALPROTECTIN IN A COHORT OF PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH ABATACEPT
Authors: S. E. L. Della Pina, S. Piantoni, E. Garrafa, M. Vezzoli, A. Caproli, L. Franzoni, I. Cavazzana, P. Airò, F. Franceschini
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The research of new biomarkers is still an unmet need in the field of rheumatoid arthritis (RA), especially for patients (pts) without rheumatoid factor and/or anti-citrullinated peptides positivity (seronegative RA), and for those without the elevation of inflammatory markers, such as the C-reactive protein (CRP) [1]. Calprotectin (CLP) is a heterodimeric complex of two calcium binding proteins which is expressed in granulocytes and monocytes. It mediates cell differentiation, activation, migration, apoptosis and the production of pro-inflammatory factors [2]. Recent studies showed that CLP synovial fluid levels are higher in RA pts and that its serum levels might directly reflect the synovitis severity [3]. Abatacept (ABA) was demonstrated to interfere with the migration of monocytes to the joint, reducing the expression of adhesion molecules via hampering actin dynamics [4]. No studies are available on the potential value of CLP as a biomarker of ABA treatment response in pts with RA. <h3>Objectives</h3> To analyse CLP levels in ABA treated RA pts. <h3>Methods</h3> Forty-three consecutive ABA treated RA pts [84% female, median age (1<sup>st</sup>-3<sup>rd</sup> quartile)=61 (52-68) years, 81% seropositive, DAS28-CRP=4.57 (3.95-5.27)] were enrolled. EULAR criteria were used to evaluate the response to the treatment after 6 months (T6). CLP serum levels (µg/ml) were measured at baseline (T0) and at T6, by a commercial kit (Quanta Flash Calprotectin assay, Werfen; cut-off value=4). <h3>Results</h3> At T0, RA pts showed increased CLP serum levels (65%) irrespective of their seropositivity (p=0.50) or the presence of elevated CRP (p=0.23). T0 CLP was not different comparing pts according to their response [good+moderate, 67% vs non-responders, 33%: 4.44 (2.68-7.64) vs 6.66 (4.80-8.71); p=0.33], even in pts with T0 normal CRP levels [5.8 (3.27-6.36) vs 4.54 (3.61-7.47); p=0.86]. CLP decreased after treatment with ABA (T0 vs T6) (4.98 (3.04-7.88) vs 3.24 (2.20-5.72); p=0.0049), both in responders [4.44 (2.68-7.64) vs 3.24 (1.90-5.64); p=0.034], and in non-responders (6.66 (4.80-8.71) vs 2.95 (2.18-4.30); p=0.039). CLP was not significantly correlated with CRP at T0 or at T6, nor with DAS28-CRP at T0, whereas a significant correlation was observed with DAS28-CRP at T6 (r=0.34; p=0.034). The T6-T0 variations of CLP and DAS28-CRP were not correlated (r=0.06; p=0.6919), even evaluating separately pts according to their response. <h3>Conclusion</h3> CLP serum levels are increased in RA pts, without differences in groups separated on the basis of their seropositive status or their CRP levels, confirming the potential role of CLP as a biomarker of RA [3, 5]. The correlation between CLP levels and the composite index at T6, but not with CRP levels, suggests a possible clinical value, independent from CRP [6]. Circulating levels of CLP, a myeloid-related protein, did not have a predictive value for the response to ABA, an agent mainly targeting lymphocytes [4]. <h3>References</h3> [1] Vermeer M et al.Arthritis Rheum 2011; [2] Jarlborg M et al.Arthritis Res Ther 2020; [3] Wang Q et al.J Transl Int Med 2019; [4] Bonelli M et al.Arthritis Rheum 2013; [5] Centola M et al.PLoS One 2013; [6] Hurkanova J et al.Clin Rheumatol 2018. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.